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Circular RNA (circRNA), a novel class of noncoding RNAs, has been used extensively to complement transcriptome remodeling in the central nervous system, although the genomic coverage provided has rarely been studied in intracerebral hemorrhage (ICH) and is limited and fails to provide a detailed picture of the cerebral transcriptome landscape. Here, we described sequencing-based transcriptome profiling, providing comprehensive analysis of cerebral circRNA, messenger RNA (mRNA) and microRNA (miRNA) expression in ICH rats. In the study, male Sprague–Dawley rats were subjected to ICH, and next-generation sequencing of RNAs isolated from non-hemorrhagic (Sham) and hemorrhagic (ICH) rat brain samples collected 7 (early phase) and 28 (chronic phase) days after insults, was conducted. Bioinformatics analysis was performed to determine miRNA binding sites and gene ontology of circRNAs, target genes of miRNAs, as well as biological functions of mRNAs, altered after ICH. These analyses revealed different expression profiles of circRNAs, mRNAs and miRNAs in day-7 and day-28 ICH groups, respectively, compared with the Sham. In addition, the expression signature of circRNAs was more sensitive to disease progression than that of mRNAs or miRNAs. Further analysis suggested two temporally specific circRNA-miRNA-mRNA networks based on the competitive endogenous RNA theory, which had profound impacts on brain activities after ICH. In summary, these results suggested an important role for circRNAs in the pathogenesis of ICH and in reverse remodeling based on self-protection support, providing deep insights into diverse possibilities for ICH therapy through targeting circRNAs. [ABSTRACT FROM AUTHOR]

Objectives: A major limitation of intracerebral haemorrhage (ICH) research is the lack of reproducible animal models. The purpose of the present study was to produce experimental haemorrhages and to characterise the lesion by histology and behaviour in rats. Methods: A total of 180 male SD rats were anaesthetised with chloral hydrate. Rats were placed in a stereotactic frame, and a microinjector was introduced through a burr hole into the right striatum. Each rat received an injection of 60 mL of semi-coagulated autologous whole blood over 6 minutes. The needle was slowly withdrawn 40 minutes after the injection. Control rat had only needle insertion. Time courses of haematoma resolution and pathological changes after intrastriatal injection of semi-coagulated autologous blood were observed. Neurological status was evaluated on days 1, 3, 5, 7, 14 and 21.The behavioural tests used were forelimb placing and a corner turn test. Results: Rats with ICH had a marked, persistent neurological deficit and a highly reproduced haematoma in shape and size. Histologically, haematoma was observed at 1, 3, 5 and 7 days and cysts at 3 weeks. Behavioural abnormalities were present for 14 days, with the recovery of function occurring during the third week. Conclusions: The present ICH model in rats produces a consistent neurological deficit and reproducible haematomain shapeand size. Thismodel couldbe useful to evaluatethe future pharmaceutical therapies in ICH. [ABSTRACT FROM AUTHOR]

Abstract To the clinical cognitive impairment following intracerebral hemorrhage, comprehensive neuropsychological assessments and efficacious interventions have rarely been conducted. Lithium chloride, a classical treatment for bipolar disorder, has shown neuroprotective effects through glycogen synthase kinase-3β inhibition in a variety of central nervous system diseases, including stroke. Since neurons that contain glutamate play crucial roles in psychological functions, such as learning and memory, the glutamate-mediated excitotoxicity and consequent neuronal death and cognitive impairment in hippocampus may co-determine the clinical course of intracerebral hemorrhage. However, the potential molecular mechanisms have rarely been demonstrated in intracerebral hemorrhage researches. In this study, Male Sprague-Dawley rats, subjected to intrastriatal blood infusion, were treated with lithium chloride and underwent neurobehavioral test for equivalent injury severity and neurological functional deficits, Morris water maze test for cognitive impairment, high performance liquid chromatography analysis for excitotoxic index determination, immunohistochemistry analysis for neuronal apoptosis, and Western blot analysis for glycogen synthase kinase-3β activity. Our results showed lithium chloride inhibited glycogen synthase kinase-3β activation, which on one hand, suppressed downstream CRMP-2/NR2B, thus diminishing the excitotoxic index level; and on the other, stabilized β-catenin, thus modulating its downstream apoptosis-related factors such as NF-κB, Bcl-2 and Bax. Meanwhile, glycogen synthase kinase-3β inactivation was paralleled by decreased neuronal death, improved neurological functional deficits and ameliorated cognitive deficits in intracerebral hemorrhage animals. These findings indicate that lithium chloride improves glutamate-mediated excitotoxicity-induced cognitive deficits after intracerebral hemorrhage and that lithium chloride might be a potential therapeutic agent for brain damages caused by intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]